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1.
Opt Express ; 31(4): 5767-5776, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36823849

RESUMO

The temporal modulation of an electron bunch train accelerated from a foil target irradiated by an intense laser pulse is studied by measuring the coherent transition radiation (CTR) from the rear surface of a target. We experimentally obtained CTR spectra from a 1 µm thick foil target irradiated at a maximum intensity of 6.5 × 1019 W/cm2. Spectral redshifts of the emitted radiation corresponding to increases in laser intensity were observed. These measurements were compared with the theoretical calculation of CTR spectra considering ultrafast surface dynamics, such as plasma surface oscillation and relativistically induced transparency. Plasma surface oscillations induce a spectral redshift, while relativistic transparency causes a spectral blueshift. Both effects are required to find reasonable agreement with the experiment over the entire range of laser intensities.

2.
Ann Oncol ; 33(4): 384-394, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35093516

RESUMO

BACKGROUND: Primary analyses of the phase III BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here, we report 4.5-year follow-up data from the trial. PATIENTS AND METHODS: Women with untreated stage II-III TNBC were randomized (2 : 1 : 1) to paclitaxel (weekly for 12 doses) plus: (i) carboplatin (every 3 weeks for four cycles) plus veliparib (twice daily); (ii) carboplatin plus veliparib placebo; or (iii) carboplatin placebo plus veliparib placebo. All patients then received doxorubicin and cyclophosphamide every 2-3 weeks for four cycles. The primary endpoint was pCR. Secondary endpoints included event-free survival (EFS), overall survival (OS), and safety. Since the co-primary endpoint of increased pCR with carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel was not met, secondary analyses are descriptive. RESULTS: Of 634 patients, 316 were randomized to carboplatin plus veliparib with paclitaxel, 160 to carboplatin with paclitaxel, and 158 to paclitaxel. With median follow-up of 4.5 years, the hazard ratio for EFS for carboplatin plus veliparib with paclitaxel versus paclitaxel was 0.63 [95% confidence interval (CI) 0.43-0.92, P = 0.02], but 1.12 (95% CI 0.72-1.72, P = 0.62) for carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel. In post hoc analysis, the hazard ratio for EFS was 0.57 (95% CI 0.36-0.91, P = 0.02) for carboplatin with paclitaxel versus paclitaxel. OS did not differ significantly between treatment arms, nor did rates of myelodysplastic syndromes, acute myeloid leukemia, or other secondary malignancies. CONCLUSIONS: Improvement in pCR with the addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, whereas adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by doxorubicin and cyclophosphamide neoadjuvant chemotherapy for early-stage TNBC.


Assuntos
Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis , Carboplatina , Ciclofosfamida , Doxorrubicina , Feminino , Seguimentos , Humanos , Paclitaxel , Neoplasias de Mama Triplo Negativas/patologia
3.
Osteoarthritis Cartilage ; 30(2): 270-279, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34800631

RESUMO

OBJECTIVE: To develop a machine learning-based prediction model for incident radiographic osteoarthritis (OA) of the knee over 8 years using MRI-based cartilage biochemical composition and knee joint structure, demographics, and clinical predictors including muscle strength and symptoms. DESIGN: Individuals (n = 1,044) with baseline Kellgren Lawrence (KL) grade 0-1 in the right knee from the Osteoarthritis Initiative database were analyzed. 3T MRI at baseline was used to quantify knee cartilage T2, and Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone marrow. The outcome was set as true if a subject developed KL grade 2-4 OA in the right knee over 8 years (n = 183) and false if the subject remained at KL 0-1 over 8 years (n = 861). We developed and compared three models: Model 1: 112 predictors based on OA risk factors; Model 2: top ten predictors based on feature importance score from Model 1 and clinical relevance; Model 3: Model 2 without the imaging predictors. We compared the models using the area under the ROC curve derived from hold-out data. RESULTS: The 10-predictor model (Model 2, that includes cartilage and meniscus WORMS scores and cartilage T2) had a slightly lower AUC (0.772) compared to the model with 112 predictors (Model 1: AUC = 0.792, p = 0.739); and had a significantly higher AUC compared to the model without MR imaging predictors (Model 3, AUC = 0.669, p = 0.011). CONCLUSIONS: A 10-predictor model including MRI parameters coupled with demographics, symptoms, muscle, and physical activity scores provides good prediction of incident radiographic OA over 8 years.


Assuntos
Articulação do Joelho/diagnóstico por imagem , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Osteoartrite do Joelho/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo
4.
Ann Oncol ; 32(5): 652-660, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33539944

RESUMO

BACKGROUND: Resistance to standard chemotherapy in metastatic triple-negative breast cancer (mTNBC) is associated with upregulation of the mitogen-activated protein kinase (MAPK) pathway. Cobimetinib, an MAPK/extracellular signal-regulated kinase (MEK) inhibitor, may increase sensitivity to taxanes and programmed death-ligand 1 inhibitors. COLET is a three-cohort phase II study evaluating first-line cobimetinib plus chemotherapy, with or without atezolizumab, in patients with locally advanced or mTNBC. PATIENTS AND METHODS: Patients were ≥18 years with locally advanced or mTNBC. Following a safety run-in, patients in cohort I were randomized 1:1 to cobimetinib (60 mg, D3-D23 of each 28-day cycle) or placebo, plus paclitaxel (80 mg/m2, D1, 8, and 15). Additional patients were randomized (1:1) to cohort II or III to receive cobimetinib plus atezolizumab (840 mg, D1 and D15) and either paclitaxel (cohort II) or nab-paclitaxel [cohort III (100 mg/m2, D1, D8, and D15)]. Primary endpoints were investigator-assessed progression-free survival (PFS) (cohort I) and confirmed objective response rate (ORR) (cohorts II/III). Safety and tolerability were also assessed. RESULTS: In the expansion stages, median PFS was 5.5 months for cobimetinib/paclitaxel versus 3.8 months for placebo/paclitaxel in cohort I [hazard ratio 0.73; 95% confidence interval (CI) 0.43-1.24; P = 0.25]. In cohort I, ORR was 38.3% (95% CI 24.40-52.20) for cobimetinib/paclitaxel and 20.9% (95% CI 8.77-33.09) for placebo/paclitaxel; ORRs in cohorts II and III were 34.4% (95% CI 18.57-53.19) and 29.0% (95% CI 14.22-48.04), respectively. Diarrhea was the most common grade ≥3 adverse events across all cohorts. CONCLUSIONS: Cobimetinib added to paclitaxel did not lead to a statistically significant increase in PFS or ORR, although a nonsignificant trend toward a numerical increase was observed. Cobimetinib plus atezolizumab and a taxane did not appear to increase ORR. This demonstrates the potential activity of a combinatorial MEK inhibitor, chemotherapy, and immunotherapy in this difficult-to-treat population.


Assuntos
Neoplasias de Mama Triplo Negativas , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azetidinas , Humanos , Paclitaxel/efeitos adversos , Piperidinas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
5.
Br J Surg ; 107(6): 687-694, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026467

RESUMO

BACKGROUND: This study evaluated the incidence, patterns and risk factors for recurrence after hemithyroidectomy in patients with low- and intermediate-risk papillary thyroid carcinoma (PTC), and verified the predictive role of the risk staging systems in current use. METHODS: The clinicopathological characteristics and risk categories were analysed according to recurrence in patients who underwent hemithyroidectomy for low- and intermediate-risk conventional PTC, and were followed up for at least 24 months. Five risk staging systems were used to stratify risk: the 2015 American Thyroid Association (ATA) system; Age, Metastases, Extent and Size (AMES) system; Metastases, Age, Complete resection, Invasion and Size (MACIS) system; Grade, Age, Metastases, Extent and Size (GAMES) system; and the eighth AJCC system. RESULTS: The study included 561 patients; 93·9 per cent of the study population (527 of 561) had a papillary thyroid microcarcinoma 1 cm or smaller in size. At a mean follow-up of 83 months, 25 patients (4·5 per cent) had recurrence; among these patients, 23 (92%) presented with a remaining thyroid lobe. Multifocality was significantly associated with recurrence in univariable and multivariable analyses (adjusted hazard ratio 3·16, 95 per cent c.i. 1·25 to 7·98; P = 0·015). Disease-free survival (DFS) varied according to multifocality (P = 0·010). The five risk staging systems were not associated with recurrence, and their Harrell's C-index ranged from 0·500 to 0·531. DFS rates did not differ between the risk categories in each system. CONCLUSION: Although the recurrence rate after hemithyroidectomy in patients with low- and intermediate-risk PTC was low, meticulous follow-up focusing on the remaining thyroid lobe is needed for early detection and timely management of recurrence. The risk scoring systems in current use have no predictive role in these patients.


ANTECEDENTES: Este estudio evaluó la incidencia, patrones y factores de riesgo de recidiva tras hemitiroidectomía en pacientes con carcinoma papilar de tiroides (papillary thyroid carcinoma, PTC) de riesgo bajo e intermedio y verificó el papel predictivo de los sistemas de estadificación del riesgo utilizados en la actualidad (risk staging systems, RSSs). MÉTODOS: Se analizaron las características clinicopatológicas y las categorías de riesgo en base a la recidiva en 561 pacientes que fueron sometidos a hemitiroidectomía por PTC convencional de riesgo bajo e intermedio y seguidos durante ≥ 24 meses. Para estratificar el riesgo se utilizaron cinco RSSs, incluyendo el sistema de la American Thyroid Association (ATA) de 2015; la edad, las metástasis, la extensión y el tamaño del sistema AMES; las metástasis, la edad, la resección completa, la invasión y el tamaño del sistema GAMES; y la octava edición de la American Joint Committee on Cancer system (AJCC). RESULTADOS: La proporción de la población de estudio con microcarcinoma papilar de tiroides de tamaño ≤ 1 cm fue 93,9% (527/561). A los 83 meses de seguimiento, 25 pacientes (4,5%) presentaron recidiva y entre estos pacientes, 23 (92%) no habían sido sometidos a tiroidectomía total. La multifocalidad se asoció significativamente con la recidiva en los análisis univariado y multivariable con un cociente de riesgos instantáneos (hazard ratio, HR) ajustado de 3,163; i.c. del 95% 1,253-7,983; P = 0,015. La supervivencia libre de enfermedad (disease-free survival, DFS) varió según la multifocalidad (P = 0,010). Los cinco RSSs no se asociaron con la recidiva, y su índice C de Harrell fue 0,500-0,531. Las DFSs no fueron diferentes entre las categorías de riesgo de cada RSS. CONCLUSIÓN: La tasa de recidiva tras hemitiroidectomía en pacientes con PTC de riesgo bajo e intermedio fue baja. Sin embargo, es necesario efectuar un seguimiento meticuloso, centrándose en el lóbulo tiroideo restante, para la detección precoz y el tratamiento oportuno de la recidiva. Los RSSs que se utilizan en la actualidad no tienen valor predictivo en estos pacientes.


Assuntos
Recidiva Local de Neoplasia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adolescente , Adulto , Idoso , Regras de Decisão Clínica , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Resultado do Tratamento , Adulto Jovem
6.
J Endocrinol Invest ; 40(3): 305-311, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27761885

RESUMO

PURPOSE: The aim of this study was to elucidate the cytological characteristics and the diagnostic usefulness of intraoperative cytology (IOC) for papillary thyroid carcinoma (PTC). In addition, using decision tree analysis, effective features for accurate cytological diagnosis were sought. METHODS: We investigated cellularity, cytological features and diagnosis based on the Bethesda System for Reporting Thyroid Cytopathology in IOC of 240 conventional PTCs. The cytological features were evaluated in terms of nuclear score with nuclear features, and additional figures such as presence of swirling sheets, psammoma bodies, and multinucleated giant cells. The nuclear score (range 0-7) was made via seven nuclear features, including (1) enlarged, (2) oval or irregularly shaped nuclei, (3) longitudinal nuclear grooves, (4) intranuclear cytoplasmic pseudoinclusion, (5) pale nuclei with powdery chromatin, (6) nuclear membrane thickening, and (7) marginally placed micronucleoli. RESULTS: Nuclear scores in PTC, suspicious for malignancy, and atypia of undetermined significance cases were 6.18 ± 0.80, 4.48 ± 0.82, and 3.15 ± 0.67, respectively. Additional figures more frequent in PTC than in other diagnostic categories were identified. Cellularity of IOC significantly correlated with tumor size, nuclear score, and presence of additional figures. Also, IOCs with higher nuclear scores (4-7) significantly correlated with larger tumor size and presence of additional figures. In decision tree analysis, IOCs with nuclear score >5 and swirling sheets could be considered diagnostic for PTCs. CONCLUSIONS: Our study suggests that IOCs using nuclear features and additional figures could be useful with decreasing the likelihood of inconclusive results.


Assuntos
Carcinoma Papilar/diagnóstico , Citodiagnóstico/métodos , Árvores de Decisões , Neoplasias da Glândula Tireoide/diagnóstico , Biópsia por Agulha Fina , Carcinoma Papilar/cirurgia , Diagnóstico Diferencial , Humanos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia
7.
Cytopathology ; 28(1): 16-23, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27245707

RESUMO

OBJECTIVE: The aims of this study were (i) to investigate the diagnostic accuracy of Papanicolaou (Pap) smears and (ii) to evaluate the clinicopathological significance of the presence of low-grade squamous intraepithelial lesion (LSIL) cells in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) cytology. METHODS: We retrospectively reviewed paired cytological and histological findings from 3141 patients. ASC-H cytology was classified as either ASC-H or LSIL with some features suggestive of the presence of a concurrent HSIL (LSIL-H). Clinicopathological characteristics were evaluated through a retrospective study and meta-analysis. RESULTS: The accuracy of the cytological diagnosis was 93.7% (2942 of 3141 cases). The positive predictive value (PPV) of ASC-H for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+ ) was 51.4%. In cases of LSIL-H, CIN 2+ histology was more prevalent in the pre-menopausal period (19-44 years) than in peri- and postmenopausal periods (older than 45 years) (P = 0.024). There was no difference in the ability of LSIL-H and ASC-H to predict CIN 2+. CONCLUSION: The Pap smear is a good cervical cancer screening method. Although there was no difference in the predictive value for CIN 2+ between LSIL-H and ASC-H, the presence of definite LSIL cells was more predictive of CIN 2+ in younger patients than in older patients.


Assuntos
Detecção Precoce de Câncer , Teste de Papanicolaou , Lesões Intraepiteliais Escamosas Cervicais/patologia , Displasia do Colo do Útero/diagnóstico , Adulto , Idoso , Células Escamosas Atípicas do Colo do Útero/patologia , Citodiagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Displasia do Colo do Útero/patologia
8.
Allergy ; 70(12): 1569-79, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26335962

RESUMO

BACKGROUND: House dust mites (HDMs) are the most important source of indoor aeroallergens that contribute to the rising incidence of allergic diseases such as allergic asthma. The major HDM, Der f 2, induces inflammatory cytokine expression. Little is known about the signaling pathway involved. OBJECTIVE: We wanted to define the Der f 2 signaling pathway from its receptor to the transcription factor responsible for IL-13 expression and production. METHODS: Human bronchial epithelial cells were stimulated with Der f 2. The release and gene expression of IL-13 were measured by means of ELISA and RT-PCR, respectively. In the airway inflammation mouse model, airway responses were assessed using ELISA, histology, BAL fluid, and methacholine responsiveness. RESULTS: Here, we show that Der f 2 binds to TLR4 and induces IL-13 expression and production. In the airway inflammation mouse model, Der f 2-induced IL-13 production significantly decreased with treatment of TAK-242, a novel TLR4 inhibitor. Activation of TLR4 by Der f 2 requires the recruitment and activation of Syk, which leads to phosphorylation of PLCγ and membrane translocation of PKCα. p38 MAPK is then activated by PKCα and stimulates PLD1 activity by phosphorylating the Thr147 residue of PLD1. PLD1 activation enhanced binding of ROCK1 to ATF-2 and leads to increased expression of IL-13. CONCLUSION: Our data extend the knowledge for a variety of possible roles of PLD1 in allergic disorders including asthma pathogenesis and suggest possible candidacy of PLD1 as a molecular target for novel therapeutic approaches.


Assuntos
Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Interleucina-13/biossíntese , Fosfolipase D/imunologia , Hipersensibilidade Respiratória/imunologia , Transdução de Sinais/imunologia , Animais , Antígenos de Dermatophagoides/metabolismo , Proteínas de Artrópodes/metabolismo , Asma/imunologia , Asma/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Ativação Enzimática/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoprecipitação , Camundongos , Fosfolipase D/metabolismo , Pyroglyphidae/imunologia , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo
9.
J Endocrinol Invest ; 37(2): 167-73, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24497215

RESUMO

BACKGROUND: Pathologically confirmed microscopic extrathyroidal extension (ETE) is often identified after hemithyroidectomy in patients with papillary thyroid microcarcinoma (PTMC). Without the presence of microscopic ETE, these patients would be optimal candidates for hemithyroidectomy. AIM: The present study aimed at evaluating the clinical impact of microscopic ETE on the recurrence of PTMC treated with hemithyroidectomy. SUBJECTS AND METHODS: We compared the clinicopathological characteristics and 5-year outcomes for 262 PTMC patients without ETE and 86 with microscopic ETE who were treated with hemithyroidectomy between January 2004 and December 2010. RESULTS: The mean tumour size was larger (0.67 vs. 0.54 cm, p < 0.001) and the proportion of tumours measuring ≥0.5 cm was higher (84.9 vs. 66.8 %, p = 0.001) in patients with microscopic ETE as compared with patients without ETE. Occult multifocal disease was more frequent in patients with microscopic ETE than in those without ETE (14.0 vs. 6.5 %, p = 0.030). However, the recurrence rate was not different between the two groups during the mean 55.8-month follow-up period. In addition, univariate and multivariate analyses revealed no meaningful association between recurrence and microscopic ETE in patients with PTMC treated with hemithyroidectomy. CONCLUSIONS: Although microscopic ETE was associated with large tumour size and multifocal disease, its clinical impact on disease recurrence was not significant in PTMC patients treated with hemithyroidectomy. Therefore, microscopic ETE identified after hemithyroidectomy would not be an absolute indication for completion thyroidectomy in patients with PTMC.


Assuntos
Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Carcinoma Papilar/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/epidemiologia , Resultado do Tratamento , Carga Tumoral
10.
Rhinology ; 52(3): 238-45, 2014 09.
Artigo em Inglês | MEDLINE | ID: mdl-25271529

RESUMO

BACKGROUND: Extraocular muscle (EOM) injury is a rare but serious complication of endoscopic sinus surgery (ESS). The aim of this study is to describe the clinical characteristics and course of EOM injury occurring during ESS. DESIGN: Retrospective case series. METHODS: Medical records and CT images of patients who suffered from EOM injury after ESS between 2006 and 2012 were retrospectively reviewed. Patient demographics, endoscopic anatomy, type of surgery (primary or revision), predisposing risk factors, site and extent of injury on CT imaging, and associated complications were evaluated. In addition, data regarding ophthalmologic management and clinical outcomes were collected. RESULTS: Ten patients with EOM injuries after ESS were included in this study. One patient was undergoing revision ESS. All patients sustained medial rectus muscle injury and one patient suffered concurrent ipsilateral inferior rectus muscle injury. A microdebrider was used in nine cases. Right-sided injury (90% of patients) was more prevalent than left-sided injury, and 70% of injured medial rectus muscles were completely transected. After subsequent strabismus surgery, 8/9 patients regained binocular single vision in primary gaze despite residual diplopia in some gaze positions. CONCLUSION: Although proper ophthalmologic surgery after EOM injury may improve deviation in the primary gaze position, none of the patients regained normal EOM movement. Therefore, prevention of this complication through adequate surgical technique and precautions is important.


Assuntos
Endoscopia/efeitos adversos , Músculos Oculomotores/lesões , Seios Paranasais/cirurgia , Adulto , Diplopia/etiologia , Diplopia/cirurgia , Endoscopia/instrumentação , Infecções Oculares Fúngicas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rinite/cirurgia , Fatores de Risco , Sinusite/cirurgia , Estrabismo/etiologia , Estrabismo/cirurgia , Adulto Jovem
11.
Ann Oncol ; 24(6): 1485-90, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23380385

RESUMO

BACKGROUND: This phase II neoadjuvant trial evaluated bevacizumab-docetaxel and carboplatin in triple-negative breast cancer. PATIENTS AND METHODS: Women with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-negative, stage II/III breast cancer received six cycles of 75 mg/m(2) docetaxel, carboplatin (AUC = 5) and 15 mg/kg bevacizumab every 21 days. The primary end point was pathological complete response (pCR) in breasts and axillary lymph nodes (ALN). RESULTS: Forty-five patients were recruited from the Korean Cancer Study Group. The median age was 45 (range 30-72) years. ALNs were positive in 80% of patients (n = 36) at diagnosis. Overall, 98% of patients (n = 44) completed therapy and underwent surgery. The pCR rate was 42% (n = 19); clinical response rate 96% (n = 43); complete 13% (n = 6); partial 82% (n = 37); stable disease 2% (n = 1). Breast-conserving surgery was undertaken in 78% of patients (n = 35). Most frequent grade 3/4 adverse events were neutropenia (84%, n = 38) and febrile neutropenia (9%, n = 4). One patient experienced delayed wound healing after surgery. CONCLUSIONS: Neoadjuvant bevacizumab, docetaxel and carboplatin resulted in an encouraging pCR rate and negligible wound healing problems after surgery.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Neoplasias da Mama/epidemiologia , Carboplatina/administração & dosagem , Docetaxel , Feminino , Humanos , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Taxoides/administração & dosagem , Resultado do Tratamento
12.
Invest New Drugs ; 31(5): 1300-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23677653

RESUMO

BACKGROUNDS: A pegylated form of recombinant granulocyte-colony stimulating factor (G-CSF) was developed for prophylactic use in breast cancer. The aim of this study was to evaluate the efficacy and safety of once-per-cycle DA-3031 in patients receiving chemotherapy for breast cancer. METHODS: A total of 61 patients receiving docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy were randomized in cycle 1 to receive daily injections of filgrastim (100 µg/m(2)) or a single subcutaneous injection of pegylated filgrastim DA-3031 at a dose of either 3.6 mg or 6 mg. RESULTS: The mean duration of grade 4 neutropenia in cycle 1 was comparable among the treatment groups (2.48, 2.20, and 2.05 days for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P=0.275). No statistically significant differences were observed in the incidence of febrile neutropenia between the treatment groups (9.5 %, 15.0 %, and 5.0 % for filgrastim, DA-3031 3.6 mg and 6 mg, respectively; P=0.681) in cycle 1. The incidences of adverse events attributable to G-CSF were similar among the treatment groups. CONCLUSIONS: Fixed doses of 3.6 mg or 6 mg DA-3031 have an efficacy comparable to that of daily injections of filgrastim in ameliorating grade 4 neutropenia in patients receiving TAC chemotherapy.


Assuntos
Medicamentos Biossimilares/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neutropenia/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Neoplasias da Mama/sangue , Ciclofosfamida/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/induzido quimicamente , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Taxoides/administração & dosagem , Resultado do Tratamento
13.
Br J Cancer ; 107(7): 1075-82, 2012 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-22918394

RESUMO

BACKGROUND: In Asia, large-scale studies on anti-HER2 treatment in HER2-positive breast cancer patients with brain metastases are limited. We studied the treatment patterns of these patients in Asia to evaluate the impact of anti-HER2 treatment on the time to occurrence of brain metastases (TTBM) and survival after brain metastasis (BM). METHODS: A retrospective study of HER2-positive breast cancer patients diagnosed with BM between January 2006 and December 2008 in six Asian countries was conducted. Demographics, tumour characteristics, treatment details, and events dates were collected from medical records. RESULTS: Data from 280 patients were analysed. Before BM, 63% received anti-HER2 treatment. These patients had significantly longer TTBM than those without anti-HER2 treatment (median 33 vs 19 months; P<0.002). After BM, 93% received radiotherapy, 57% received chemotherapy, and 41% received anti-HER2 treatment (trastuzumab and/or lapatinib). Use of both anti-HER2 agents, primarily sequentially, after BM demonstrated the longest survival after BM and was associated with a significant survival benefit over no anti-HER2 treatment (median 26 vs 6 months; hazard ratio 0.37; 95% CI 0.19-0.72). CONCLUSION: Anti-HER2 treatment before BM was associated with longer TTBM. Anti-HER2 treatment after BM was associated with a survival benefit, especially when both trastuzumab and lapatinib were utilised.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/patologia , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Feminino , Humanos , Lapatinib , Pessoa de Meia-Idade , Quinazolinas/uso terapêutico , Receptor ErbB-2/biossíntese , Estudos Retrospectivos , Trastuzumab , Adulto Jovem
14.
Cephalalgia ; 30(12): 1514-23, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20974583

RESUMO

BACKGROUND: Tension-type headache (TTH) is a headache in which musculoskeletal impairments of the craniocervical region may play an important role in its pathogenesis. We investigated the presence of myofascial, postural and mechanical abnormalities in patients with frequent episodic and chronic tension-type headache (ETTH and CTTH, respectively). METHODS: The study population consisted of 36 patients with ETTH, 23 with CTTH and 42 control subjects. Myofascial trigger points (MTrPs) were identified in the upper trapezius, sternocleidomastoid, temporalis and suboccipital muscles. Sagittal C7-tragus angle was measured to evaluate flexor head posture (FHP), and neck mobility was assessed using an inclinometer. RESULTS: Only active MTrPs were significantly different between the ETTH and CTTH groups (p < .001). Patients with CTTH showed a larger sagittal C7-tragus angle (p = .011), that is, greater FHP and restricted neck mobility for both rotations compared to controls (p < .001). Although active MTrPs were correlated with the frequency and duration of headache, no correlations were observed for FHP or neck mobility. CONCLUSION: Active MTrPs in the craniocervical region contribute to triggering or maintenance of TTH and posture or neck mobility may be a result of chronic headache.


Assuntos
Síndromes da Dor Miofascial/fisiopatologia , Pescoço/fisiopatologia , Postura , Ombro/fisiopatologia , Cefaleia do Tipo Tensional/fisiopatologia , Feminino , Humanos , Masculino
15.
Clin Exp Allergy ; 39(4): 602-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19178543

RESUMO

BACKGROUND: The ant species Pachycondyla chinensis, which has spread from Far Eastern Asia to New Zealand and North America, induces anaphylactic reactions in human with its sting. However, the major allergens of P. chinensis have not yet been characterized. METHODS: We selected seven patients with histories of anaphylaxis induced by P. chinensis. Two-dimensional electrophoresis (2-DE) was used to identify the major allergens. We subsequently performed Western blots for P. chinensis-specific IgEs, N-terminal amino acid sequencing, ESI-MS/MS, and RT-PCR using primers based on the N-terminal sequence. RESULTS: Six of the anaphylactic subjects had an IgE specific to a 23 kDa allergen of P. chinensis. Two candidates for major allergens, 23 kDa (pI 8.7) and 25 kDa (pI 6.2), were revealed by 2-DE using P. chinensis-specific IgE immunoblotting. In N-terminal sequencing and ESI-MS/MS analysis, 23 kDa (pI 8.7) and 25 kDa (pI 6.2) allergens, belonging to the protein families of antigen 5, were identified and share marked amino acid sequence similarity. The 23 kDa allergen is 206 amino acids in length and homology searches showed 54.0% and 50.0% homology with Sol i 3 and Ves v 5, respectively. CONCLUSION: The major allergens of P. chinensis are 23 kDa (pI 8.7) and 25 kDa (pI 6.2) proteins that belong to the antigen 5 family of proteins.


Assuntos
Alérgenos/química , Alérgenos/imunologia , Anafilaxia/imunologia , Formigas/imunologia , Mordeduras e Picadas de Insetos/imunologia , Adulto , Alérgenos/isolamento & purificação , Sequência de Aminoácidos , Animais , Clonagem Molecular , Eletroforese em Gel Bidimensional , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Espectrometria de Massas por Ionização por Electrospray
16.
Br J Oral Maxillofac Surg ; 56(5): 406-410, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29678374

RESUMO

We report the design of a new V-shaped incision for parotidectomy that involves only preauricular and postauricular incisions and no hairline or upper cervical incision. It can be used to approach almost all the superficial parotid region, including the superior and anterior divisions, with minimal scarring. To evaluate its technical feasibility, safety, and cosmetic results, we prospectively enrolled 15 patients (between September 2015 and September 2016) who had partial parotidectomy as the primary treatment for benign parotid tumours. Operations were successfully completed through this approach alone in 14 (mean (range) operating time: 120 (105-142) minutes; drainage volume: 51 (23-70) ml; and duration of drainage: 2.6 (2-4) days). There were no serious complications such as paralysis of the facial nerve or necrosis of the wound. The mean (range) visual analogue scale (VAS) and Vancouver Scar Scale scores for the scars were 9 (8-10) and 0.9 (0-3), respectively. A V-shaped incision for partial parotidectomy is technically feasible and safe, and can produce good cosmetic results in selected patients with benign parotid tumours. Our results need to be confirmed in larger studies and case-control trials.


Assuntos
Dissecação/métodos , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia , Adulto , Idoso , Cicatriz/prevenção & controle , Drenagem , Estética , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Satisfação do Paciente , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Fatores de Tempo , Escala Visual Analógica
17.
Dig Liver Dis ; 38(7): 515-7, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16330268

RESUMO

A diospyrobezoar is a type of phytobezoar that is considered to be harder than any other types of phytobezoars. Here, we describe a new treatment modality, which effectively and easily disrupted huge gastric diospyrobezoars. A 41-year-old man with a history of diabetes mellitus was admitted with lower abdominal pain and vomiting. Upper gastrointestinal endoscopy revealed three huge, round diospyrobezoars in the stomach. He was made to drink two cans of Coca-Cola every 6 h. At endoscopy the next day, the bezoars were partially dissolved and turned to be softened. We performed direct endoscopic injection of Coca-Cola into each bezoar. At repeated endoscopy the next day, the bezoars were completely dissolved.


Assuntos
Bezoares/patologia , Bezoares/terapia , Bebidas Gaseificadas , Diospyros/efeitos adversos , Gastropatias/patologia , Gastropatias/terapia , Administração Oral , Adulto , Bezoares/dietoterapia , Bezoares/etiologia , Endoscopia , Humanos , Masculino , Gastropatias/dietoterapia
18.
Dig Liver Dis ; 38(9): 668-72, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16790371

RESUMO

BACKGROUND: Previous studies on colorectal cancer risk suggest that obesity, serum lipids and glucose might be related to colorectal carcinogenesis. This case-control study was conducted to investigate the association between obesity, serum lipids and glucose, and the risk of advanced colorectal adenoma and cancer. METHODS: Patients with histologically confirmed colorectal cancers (n=105), same number of patients with advanced colorectal adenomas matched by age and sex, and the same number of controls matched by age and sex were selected in Hanyang University Guri Hospital between January 2002 and June 2004. RESULTS: Adenoma and cancer group showed significantly higher levels of mean body mass index and serum glucose. Cancer group also showed significantly lower mean serum lipids levels than controls. We used an unordered polytomous logistic model to calculate multivariate odds ratios for advanced adenoma and cancer relative to controls. Higher serum glucose level was more strongly associated with increased risk of cancer relative to controls (odds ratio, 3.0; 95% confidence interval, 0.9-9.8) than with increased risk of advanced adenoma (odds ratio, 2.1; 95% confidence interval, 0.9-5.4). Higher body mass index was strongly associated with increased risk of advanced adenoma (odds ratio, 10.8; 95% confidence interval, 4.6-25.3), but associated with attenuated risk of cancer (odds ratio, 2.3; 95% confidence interval, 0.9-5.8). Serum triglycerides and cholesterol levels were strongly associated with reduced risk of cancer (odds ratio, 0.3; 95% confidence interval, 0.1-0.8 and odds ratio, 0.2; 95% confidence interval, 0.1-0.6, respectively). CONCLUSIONS: Obesity and hyperglycaemia are positively related to advanced colorectal adenoma formation. Furthermore, hyperglycaemia plays an important role in progression to cancer. Findings on an inverse relationship between serum triglyceride and cholesterol levels and the risk of colorectal cancer may be the secondary results from metabolic or nutritional changes in advanced colorectal cancer patients and should be clarified in further studies.


Assuntos
Pólipos Adenomatosos/sangue , Pólipos Adenomatosos/complicações , Glicemia/análise , Neoplasias Colorretais/sangue , Neoplasias Colorretais/complicações , Lipídeos/sangue , Obesidade/complicações , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Hiperglicemia/sangue , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
20.
Int J Impot Res ; 28(5): 184-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27278664

RESUMO

Three decades of research have investigated brain processing of visual sexual stimuli with neuroimaging methods. These researchers have found that sexual arousal stimuli elicit activity in a broad neural network of cortical and subcortical brain areas that are known to be associated with cognitive, emotional, motivational and physiological components. However, it is not completely understood how these neural systems integrate and modulated incoming information. Therefore, we identify cerebral areas whose activations were correlated with sexual arousal using event-related functional magnetic resonance imaging and used the dynamic causal modeling method for searching the effective connectivity about the sexual arousal processing network. Thirteen heterosexual males were scanned while they passively viewed alternating short trials of erotic and neutral pictures on a monitor. We created a subset of seven models based on our results and previous studies and selected a dominant connectivity model. Consequently, we suggest a dynamic causal model of the brain processes mediating the cognitive, emotional, motivational and physiological factors of human male sexual arousal. These findings are significant implications for the neuropsychology of male sexuality.


Assuntos
Nível de Alerta/fisiologia , Encéfalo/fisiologia , Literatura Erótica/psicologia , Rede Nervosa/fisiologia , Comportamento Sexual/fisiologia , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Heterossexualidade , Humanos , Imageamento por Ressonância Magnética , Masculino , Modelos Neurológicos , Motivação/fisiologia , Rede Nervosa/diagnóstico por imagem , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Estimulação Luminosa , Comportamento Sexual/psicologia , Adulto Jovem
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